High-Speed Sequential DNA Computing Using a Solid-State\nDNA Origami Register

DNA computing leverages\nmolecular reactions to achieve diverse\ninformation processing functions. Recently developed DNA origami registers,\nwhich could be integrated with DNA computing circuits, allow signal\ntransmission between these circuits, enabling DNA circuits to perform\ncomplex tasks in a sequential manner, thereby enhancing the programming\nspace and compatibility with various biomolecules of DNA computing.\nHowever, these registers support only single-write operations, and\nthe signal transfer involves cumbersome and time-consuming register\nmovements, limiting the speed of sequential computing. Here, we designed\na solid-state DNA origami register that compresses output data from\na 3D solution to a 2D surface, establishing a rewritable register\nsuitable for solid-state storage. We developed a heterogeneous integration\narchitecture of liquid-state circuits and solid-state registers, reducing\nthe register-mediated signal transfer time between circuits to less\nthan 1 h, thereby achieving fast sequential DNA computing. Furthermore,\nwe designed a trace signal amplifier to read surface-stored signals\nback into solution. This compact approach not only enhances the speed\nof sequential DNA computing but also lays the foundation for the visual\ndebugging and automated execution of DNA molecular algorithms.